Ion
exchange and pH controlled drug delivery systems
Session Objectives
By the end of this session, students will be able to:
• Explain the role of ion exchange resins in
the formulation of CRDF
• Discuss factors affecting the drug release
and pharmaceutical applications of IER delivery systems
• Describe the process of pH variable on the
drug release from the dosage form
• Apply the principles of ion exchange resins
and pH dependent in dosage form
development
Definition
• Ion
exchange is a reversible process in which ions of like sign are exchanged
between liquid and solid when in contact with a highly insoluble body. The drug
is released from the resinate by exchanging with ions in the gastrointestinal fluid, followed
by drug diffusion Due to the presence of high molecular weight water insoluble
polymers, the resins are not absorbed by the body and are therefore inert
Advantages
• Ion-exchange
systems are advantageous for drugs that are highly susceptible to degradation by enzymatic process
• A
major advantage of ion exchange system is low running cost
• It
requires little energy and the regenerated chemicals are cheap
• well
maintained, resin beds can last for many years before replacement
Limitations
• Limitation
is that the release rate is proportional to the concentration of the ions present in the area of administration
• The
release rate of drug can be affected by variability in diet, water intake and
individual intestinal content
Classification of Ion exchange resin
1. Cation
exchange resin
a) Strong acid
b) Weak acid
2. Anion exchange resin
a) Strong base
b) Weak base
Ion Exchangers
Naturally occurring and synthetic
• Inorganic
ion exchangers have greater selectivity and better disposal options than
organic resin
• Organic
ion exchangers are reliable and efficient in water coolant systems
• Mineral
compounds such as bentonite, Kaolinite and Illite and Zeolites such as analcite, chabazite, sodalite and
clinoptilolite are naturally occurring
inorganic ion exchangers
• Zeolites,
Titanates and silico-titanates, transition metal hexacyanoferrates are inorganic synthetic ion exchangers
• Polysaccharides
such as cellulose, algic acid, straw and peat, proteins such as casein, keratin and collagen and carbonaceous
materials such as charcoals, liquites and
coals are naturally occurring organic ion exchangers
Role of IER in Controlled Drug Delivery Systems
• The
major drawback of controlled release is dose dumping, resulting in increased
risk of toxicity
• The
usage of IER during the development of controlled release formulations plays
a significant role because of their drug
retarding properties and prevention of dose
dumping
• The
drug resinates can also be used as a drug reservoir, which has caused a change
of the drug release in hydrophilic
polymer tablets
• The
use of IER into drug delivery systems includes physico-chemical stability,
inert nature, uniform size, spherical
shape assisting coating and equilibrium driven reproducible drug release in ionic environment
• Drug
molecules attached to the resins are released by appropriate charged ions
in the gastrointestinal tract, followed
by diffusion of free drug molecules out of the
resin as shown below
Resin-
Drug + + X + à
Resin-…. X + + Drug +
Resin+
Drug – + Y – à
Resin+… Y – + Drug –
Where, X and Y are ions in the gastrointestinal tract.
• IER
have been used as drug carriers in pharmaceutical dosage forms for
controlled release formulation
• The
prolonged release of the active drug is accomplished by providing a semi- permeable coating around discrete, minute,
ion exchange resin particles with which
the drug component has been complexed to form an insoluble drug resin
complex
• The
physical and chemical properties of the IER will release the drug more uniformly than that of simple matrix formulations
Important Properties of IER
Ø Particle
size and form
Ø Porosity
and swelling
Ø Cross
linkage
Ø Available
capacity
Ø Acid
base strength
Ø Stability
Ø Purity
and toxicity
Applications of IER
Pharmaceutical applications
• Taste
masking
• Eliminating
polymorphism
• Improving
the dissolution of poorly soluble drugs
• Improving
stability
• Improving
physical characteristics
Drug delivery applications
• Oral
drug delivery
• Nasal
drug delivery
• Transdermal
drug delivery
• Ophthalmic
drug delivery
Introduction to pH controlled systems
The variable nature of the chemical environment throughout
the length of the GIT is a further constraint on dosage form design.
Drugs administered orally would encounter a spectrum of pH
ranging from 7 in mouth, 1-4 in the stomach, and 5-7 in the small intestine.
Since most drugs are either weak acids or weak bases, their
release from formulation is pH dependent.
This type of system is designed for the controlled release
of acidic (or basic) drugs in GIT at a rate independent of the variation in GI
pH by formulating them with sufficient buffering agents.
It is prepared by first blending an acidic (or basic)
drug with one or more buffering agents,
e.g. a primary, secondary, or tertiary salt of
citric acid, granulating with appropriate excipients to form small granules, and then coating the granules with
GI fluid-permeable film-forming polymer,
e.g. cellulose derivatives.
Salts of amino acids, citric acid, phosphoric acid or
tartaric acid are commonly used.
The polymer coating controls the permeation of GI fluid. The
GI fluid permeating into the device is adjusted by the buffering agents to an
appropriate constant pH, at which the drug dissolves and is delivered through
the membrane at a constant rate regardless of the location of the device in the
alimentary canal.
pH
Activated Drug Release
• This
type of drug delivery permits targeting the delivery in a region with selected
pH
• In
this system the gastro intestine liable drug is coated with an intestinal fluid soluble and insoluble
polymer i.e. Ethyl cellulose and Hydroxy
Methyl Cellulose Phthalate (HMCP)
• The
HMCP polymer gets degraded in the small intestine and produces pores in the ethyl cellulose polymer coating
• The
drug then releases from the micro porous membrane at a controlled rate
Summary
• Ion
exchange is a reversible process in which ions of like sign are exchanged between liquid and solid when in
contact with a highly insoluble body
• The
drug is released from the resinate by exchanging with ions in the gastrointestinal
fluid, followed by drug diffusion
• The
use of IER into drug delivery systems includes physico-chemical stability, inert nature, uniform size and
spherical shape which exhibits
reproducible drug release in ionic environment
• The
physical and chemical properties of the IER will release the drug more
uniformly than that of simple matrix formulations
• The
pharmaceutical applications of IER controlled delivery systems includes : taste masking of drug, improving
dissolution of poorly soluble drugs,
physical characteristics and stability
• pH
activated drug delivery permits targeting the drug release in a region with selected pH. It is designed for
the controlled release of acidic or
basic drugs independent of G.I. pH variablity
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